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Non-typhoidal Salmonella strains are responsible for invasive infections associated with high mortality and recurrence in sub-Saharan Africa, and there is strong evidence for clonal relapse following antibiotic treatment. Persisters are non-growing bacteria that are thought to be responsible for the recalcitrance of many infections to antibiotics. Toxin–antitoxin systems are stress-responsive elements that are important for Salmonella persister formation, specifically during infection. Here, we report the analysis of persister formation of clinical invasive strains of Salmonella Typhimurium and Enteritidis in human primary macrophages. We show that all the invasive clinical isolates of both serovars that we tested produce high levels of persisters following internalization by human macrophages. Our genome comparison reveals that S . Enteritidis and S . Typhimurium strains contain three acetyltransferase toxins that we characterize structurally and functionally. We show that all induce the persister state by inhibiting translation through acetylation of aminoacyl-tRNAs. However, they differ in their potency and target partially different subsets of aminoacyl-tRNAs, potentially accounting for their non-redundant effect. The recalcitrance of many infections to antibiotic treatment may be due to the presence of ‘persisters’, or non-growing, antibiotic-tolerant bacteria. Here, the authors study the structures and functions of aminoacyl-tRNA acetyltransferase toxins, and their roles in persister formation in Salmonella .

The hallmark of Salmonella Typhimurium infection is an acute intestinal inflammatory response, which is mediated through the action of secreted bacterial effector proteins. The pro-inflammatory Salmonella effector SopA is a HECT-like E3 ligase, which was previously proposed to activate host RING ligases TRIM56 and TRIM65. Here we elucidate an inhibitory mechanism of TRIM56 and TRIM65 targeting by SopA. We present the crystal structure of SopA in complex with the RING domain of human TRIM56, revealing the atomic details of their interaction and the basis for SopA selectivity towards TRIM56 and TRIM65. Structure-guided biochemical analysis shows that SopA inhibits TRIM56 E3 ligase activity by occluding the E2-interacting surface of TRIM56. We further demonstrate that SopA ubiquitinates TRIM56 and TRIM65, resulting in their proteasomal degradation during infection. Our results provide the basis for how a bacterial HECT ligase blocks host RING ligases and exemplifies the multivalent power of bacterial effectors during infection. The HECT-like E3 ligase SopA in Salmonella has been suggested to activate host RING ligases TRIM56 and TRIM65. Here, the authors use mass spectrometry, crystal structures and biochemistry to examine the interactions between these proteins in detail.

Background: The aim of this study was to investigate the prevalence of plasmid-mediated quinolone resistance (PMQR) and mutations in quinolone resistance-determining regions (QRDRs) of Salmonella and their association with fluoroquinolone susceptibility in Korea. Methods: A total of 284 nonduplicated clinical isolates of Salmonella were collected from various clinical specimens at 12 tertiary-care hospitals in Korea. The qnrA, qnrB, and qnrS genes were detected by multiplex polymerase chain reaction (PCR). The qepA and aac(6′)-Ib-cr genes were amplified by PCR. The QRDRs of gyrA, gyrB, parC, and parE were amplified by PCR from the DNA of selected nalidixic acid-resistant and qnr-positive isolates. Results: We detected six qnr-positive Salmonella (four qnrS1 and two qnrB19) and one aac(6′)-Ib-cr–positive strain. A mutation in the QRDR of gyrA only (N=46) was the most common, followed by gyrA+parC (N=9), parC (N=7), gyrA+parE (N=3), parC+parE (N=3), gyrA+gyrB (N=2), and parE (N=1). There were seven novel mutations in the QRDR regions of gyrB, parC, and parE. Six of seven PMQR-positive isolates had high-level resistance to nalidixic acid, and all six strains had reduced susceptibility to ciprofloxacin. One qnrS1-positive isolate was resistant to ciprofloxacin, norfloxacin, and nalidixic acid. The resistant rates to nalidixic acid, ciprofloxacin, norfloxacin, and levofloxacin were 49.3%, 1.1%, 0.7%, and 0.4%, respectively. Conclusion: We report the first detection of PMQR in Salmonella isolates from Korea. It is essential to continue surveillance and to watch for the spread of PMQR in Salmonella for public health control.

Regulated cell death is an integral part of life, and has broad effects on organism development and homeostasis 1 . Malfunctions within the regulated cell death process, including the clearance of dying cells, can manifest in diverse pathologies throughout various tissues including the gastrointestinal tract 2 . A long appreciated, yet elusively defined relationship exists between cell death and gastrointestinal pathologies with an underlying microbial component 3 – 6 , but the direct effect of dying mammalian cells on bacterial growth is unclear. Here we advance a concept that several Enterobacteriaceae, including patient-derived clinical isolates, have an efficient growth strategy to exploit soluble factors that are released from dying gut epithelial cells. Mammalian nutrients released after caspase-3/7-dependent apoptosis boosts the growth of multiple Enterobacteriaceae and is observed using primary mouse colonic tissue, mouse and human cell lines, several apoptotic triggers, and in conventional as well as germ-free mice in vivo. The mammalian cell death nutrients induce a core transcriptional response in pathogenic Salmonella , and we identify the pyruvate formate-lyase-encoding pflB gene as a key driver of bacterial colonization in three contexts: a foodborne infection model, a TNF- and A20-dependent cell death model, and a chemotherapy-induced mucositis model. These findings introduce a new layer to the complex host–pathogen interaction, in which death-induced nutrient release acts as a source of fuel for intestinal bacteria, with implications for gut inflammation and cytotoxic chemotherapy treatment. Intestinal microorganisms exploit nutrients released by apoptotic gut epithelial cells for growth.

A cross-sectional live bird market (LBM) survey was conducted to determine the prevalence and distribution of extended-spectrum β-lactamase (ESBL)-producing and carbapenem-resistant (CR) E. coli and Salmonella spp. in retail chicken meat and LBM sewage in Bangladesh. E. coli and Salmonella spp. were identified using culture-based and molecular methods. Isolates were tested for CR by a disk diffusion test; a confirmatory ESBL screening was performed by double disk synergy test. The isolates were screened for ESBL and CR genes using PCR. Prevalence of ESBL- E. coli and Salmonella spp. in retail chicken meat was 70% and 43.4%, respectively while in LBM sewage, it was 79.7% and 28.1%, respectively. Carbapenem resistance was also common, detected in 54.1% and 46.9% of E. coli and 37.2% and 12.5% of Salmonella spp. isolated from retail chicken meat and LBM sewage, respectively. Molecular analysis revealed the presence of ESBL and CR genes, including bla CTX-M-1 , bla CTX-M-2 , and bla NDM-1 . The bla CTX-M-1 gene was detected at low frequencies among ESBL- E. coli from retail chicken meat (1.3%) and LBM sewage (3.9%), and among ESBL- Salmonella spp. from retail chicken meat (3.6%), while bla CTX-M-2 was identified in a single ESBL- E. coli isolate from LBM sewage. Notably, bla NDM-1 was detected in 5.2% of CR- E. coli and 33.6% of CR- Salmonella spp. from retail chicken meat. Multidrug resistance (MDR) was observed in 98.2% and 92.2% of ESBL- E. coli , and 97.8% and 94.4% of ESBL- Salmonella spp. from retail chicken meat and LBM sewage, respectively; while, 98.8% and 100% of CR- E. coli , and 97.5% and 87.5% of CR- Salmonella spp. from both types of samples, respectively were MDR. These results highlight the urgent need for strengthened antibiotic stewardship, regular surveillance, and improve biosecurity in live bird markets in Bangladesh.

Salmonella Heidelberg is commonly reported in foodborne outbreaks around the world, and chickens and poultry products are known as important source of these pathogen. Multidrug-resistant S. Heidelberg strains are disseminated into poultry production chair, which can lead to severe clinical infections in humans and of difficult to treat. This study aimed at evaluating the β-lactam susceptibility and genotypic relatedness of Salmonella Heidelberg at Brazilian poultry production chain. Sixty-two S. Heidelberg strains from poultry production chain (poultry, poultry meat and poultry farm) were used. All strains were evaluated to antimicrobial susceptibility by diffusion disk test, as well as β-lactam resistance genes. Genotypic relatedness was assessed by Pulsed-Field Gel Eletrophoresis, using Xba1 restriction enzyme. Forty-one strains were characterized as multidrug-resistant according to phenotype characterization. The resistance susceptibility revealed 31 distinct profiles, with higher prevalence of streptomycin (61/62), nalidixic acid (50/62), tetracycline (43/62) and β-lactam drugs (37/62). blaCMY-2 was the more frequent β-lactamase gene found (38/62); other resistance genes found were blaCTX-M (2/62), blaSHV (3/62) and blaTEM-1 (38/62). No carbapenemase genes was found. The Pulsed-Field Gel Electrophoresis showed 58 different profiles. Strains with a larger number of antimicrobial resistance were grouped into ten major clusters apart from others. The spread of resistance by ampC continues to rise, thereby turning concern to public health, since the β-lactam antimicrobials are used as a therapeutic treatment in humans.

GCN5-related N -acetyl-transferase (GNAT)-like enzymes from toxin–antitoxin modules are strong inhibitors of protein synthesis. Here, we present the bases of the regulatory mechanisms of ataRT , a model GNAT-toxin–antitoxin module, from toxin synthesis to its action as a transcriptional de-repressor. We show the antitoxin (AtaR) traps the toxin (AtaT) in a pre-catalytic monomeric state and precludes the effective binding of ac-CoA and its target Met-transfer RNA fMet . In the repressor complex, AtaR intrinsically disordered region interacts with AtaT at two different sites, folding into different structures, that are involved in two separate functional roles, toxin neutralization and placing the DNA-binding domains of AtaR in a binding-compatible orientation. Our data suggests AtaR neutralizes AtaT as a monomer, right after its synthesis and only the toxin–antitoxin complex formed in this way is an active repressor. Once activated by dimerization, later neutralization of the toxin results in a toxin–antitoxin complex that is not able to repress transcription. Structural and biochemical analysis of the AtaR–AtaT toxin–antioxin system reveals that AtaR traps AtaT in a precatalytic monomeric state and forms a heterohexameric complex to neutralize AtaT and repress transcription of the operon.

Background The global rise of multidrug-resistant (MDR) and extended-spectrum β-lactamase–producing (ESBL) Salmonella undermines treatment efficacy and threatens public health, particularly in low-resource settings. In Nigeria, data on resistance mechanisms in clinical isolates remain sparse. This study evaluates whether resistance genes and antibiogram profiles can reliably predict MDR and ESBL phenotypes to enhance early detection and surveillance. Methods This cross-sectional, laboratory-based study was conducted from January-December 2024 and analyzed 265 clinical samples (241 faecal, 24 blood) from patients with suspected enteric fever at a Nigerian tertiary hospital. Sixty-five Salmonella isolates were identified via convenience sampling using standard microbiological methods and tested for antibiotic susceptibility using the Kirby–Bauer disk diffusion method, per CLSI guidelines. ESBL production was screened by Double Disc Synergy Test, and PCR assays were performed to detect blaTEM , blaSHV, tetA , qnrA/B , and sul1 genes. MDR was defined as resistance to ≥ 3 antibiotic classes. Statistical analyses included chi-square tests, logistic regression (α = 0.05), and machine learning models: Classification and Regression Trees (CART), and Random Forest. SHAP (Shapley Additive Explanations) was used for interpretability. Results Salmonella was isolated in 65 of 265 samples (26.9%), all from fecal specimens. Resistance was highest to amoxicillin/clavulanic acid (98.5%), tetracycline (96.9%), and sulfamethoxazole/trimethoprim (90.8%) while imipenem and polymyxin B remained effective with 96.9% and 95.4% susceptibility rate respectively. ESBL production was confirmed in 18 isolates (27.7%), while 28 (43.1%) met MDR criteria. The MDR rate was 89.2%, with a mean multiple antibiotic resistance index (MARI) of 0.52. BlaTEM (77.8%), tetA (72.2%), and sul1 (61.1%) were the most prevalent resistance genes. ESBL status was strongly associated with MDR (aOR:4.6; 95%CI:1.5–14.3; p  < 0.01). CTX resistance, blaTEM , tetA , and sul1 demonstrated the strongest predictive power for MDR, with respective AUCs of 0.91, 0.88, 0.82, and 0.78. These markers consistently ranked highest across multiple predictive modelling approaches, with SHAP analysis confirming their dominant contribution to MDR classification. Conclusion Resistance genes and antibiogram markers—particularly blaTEM and CTX resistance—predict MDR and ESBL status reliably. Leveraging these markers through machine learning—combined with SHAP-based interpretability—enables early, accurate detection and supports targeted antimicrobial interventions in resource-limited settings. Clinical trial Not applicable.

We analyzed the prevalence of resistance to extended-spectrum cephalosporins (ESCs) among clinical strains of Salmonella enterica collected by the Laboratory of Clinical Microbiology in the University Clinical Hospital Lozano Blesa in the region of Aragón (Spain), for which very few epidemiological information exists. A total of 2,092 strains of S. enterica were identified in stool samples from patients with gastroenteritis. Five isolates showed an extended-spectrum beta-lactamase (ESBL) phenotype: four isolates of S. enterica serotype Virchow harbored the ESBL-encoding blaCTX-M-9 gene and an isolate of serotype Enteritidis carried a blaCTX-M-1 gene, which, to the best of our knowledge, is described here for the first time in this serotype of S. enterica. The five ESC-resistant isolates were also resistant to spectinomycin, streptomycin, kanamycin, sulfonamides, tetracycline, and trimethoprim as well as to nalidixic acid. The ESBL isolate of serotype Enteritidis, however, remained susceptible to kanamycin and nalidixic acid. A class 1 integron of 1.5 kb was detected for the four serotype Virchow isolates with the gene cassette dfrA16–aadA2. The blaCTX-M-9 gene was carried by an ∼300-kb IncHI2 conjugative plasmid in the case of the S. enterica serotype Virchow isolates. The blaCTX-M-1 gene was carried by an ∼100-kb IncI1-N conjugative plasmid for the serotype Enteritidis ESC-resistant isolate. All the four ESC-resistant strains of S. enterica serotype Virchow clustered together in a XbaI pulsed-field gel electrophoresis, which also revealed a strong similarity between them and some pulsotypes of S. enterica serotype Virchow from France.

New antibiotics are urgently needed to control infectious diseases. Metabolic enzymes could represent attractive targets for such antibiotics, but in vivo target validation is largely lacking. Here we have obtained in vivo information about over 700 Salmonella enterica enzymes from network analysis of mutant phenotypes, genome comparisons and Salmonella proteomes from infected mice. Over 400 of these enzymes are non-essential for Salmonella virulence, reflecting extensive metabolic redundancies and access to surprisingly diverse host nutrients. The essential enzymes identified were almost exclusively associated with a small subgroup of pathways, enabling us to perform a nearly exhaustive screen. Sixty-four enzymes identified as essential in Salmonella are conserved in other important human pathogens, but almost all belong to metabolic pathways that are inhibited by current antibiotics or that have previously been considered for antimicrobial development. Our comprehensive in vivo analysis thus suggests a shortage of new metabolic targets for broad-spectrum antibiotics, and draws attention to some previously known but unexploited targets. Salmonella 's Strengths In an experiment designed to reveal possible targets for antimicrobials, a combination of mutant phenotype analysis, proteomics and genome comparisons was used to determine the metabolic network of Salmonella during typhoid fever and gastroenteritis infections in mice. Because of the presence of many redundant pathways, Salmonella metabolism is surprisingly robust and only 126 enzymes were identified as essential for Salmonella virulence. Of these, thirteen are promising unexploited drug targets. Focusing on these targets might accelerate development of urgently needed antibiotics active against Salmonella . A combination of mutant phenotype analysis, genome comparisons and proteomics has elucidated the metabolic network of Salmonella during typhoid fever and enteritis infections. Owing to many redundant pathways, Salmonella metabolism is surprisingly robust, thus severely limiting the number of new drug targets.